BCMA/CD3 BiTE for RRAL or NDAL Amyloidosis With Insufficient Depth of Hematologic Response After Induction Therapy

Prior treatment

• Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy, after excluding AL amyloidosis-related peripheral neuropathy
• Medically documented cardiac syncope, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease
• Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or have not fully recovered from the surgery, or surgery is arranged during the study period
• Received live attenuated vaccine within 4 weeks prior to study treatment

Other illness

• Known intolerance, hypersensitivity, or contraindication to BCMA BiTE cellular products
• Ongoing or active infection, known HIV-positive status, or active hepatitis B or C infection
• According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.
  • Necessary medication or supportive therapy is contraindicated with study treatment.
  • Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme.

Other

• Non-AL amyloidosis, including hereditary amyloidosis
• Diagnosed with multiple myeloma, according to the International Myeloma Working Group criteria
• Have been exposed to BCMA-targeted treatment
• Women who are pregnant or breastfeeding

• Male or female patients aged 18 years or older
• Biopsy-proven diagnosis of AL amyloidosis, according to the following standard criteria:
• Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
• If clinical and laboratory parameters are insufficient to establish AL amyloidosis, or in cases of doubt, amyloid typing may be necessary
• Provide informed consent form
• Measurable disease, as defined by serum differential free light-chain concentration (dFLC; defined as the difference between amyloid forming [involved] and nonamyloid forming [uninvolved] free light-chain [FLC]) ≥50 mg/L)
• Received at least one prior line of therapy
• Must have been exposed to CD38 mAb
• Relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy
• Relapsed is defined as documented progressive disease >60 days after the last dose of prior therapy
• Refractory is defined as the documented absence of a hematologic response or hematologic progression on or within 60 days after the last dose of prior therapy
• Insufficient depth of hematologic response is defined as less than hematological PR by 2 cycles or less than hematologic VGPR by 4 cycles
• Eastern Cooperative Oncology Group performance status ≤3
• Clinical laboratory values:
• Absolute neutrophil count ≥1000/µL
• Platelet count ≥75,000/µL
• Hemoglobin ≥75g/L
• Total bilirubin ≤1.5× the upper limit of normal (ULN), except for patients with Gilbert's syndrome (as defined by >80% unconjugated bilirubin and total bilirubin ≤6 mg/dL)
• Alkaline phosphatase ≤5× ULN
• Alanine aminotransferase or aspartate aminotransferase ≤3× ULN
• Calculated creatinine clearance ≥30 mL/min
• The woman is not breastfeeding, is not pregnant, and agrees not to be pregnant during the study period and for the following 12 months.
• Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.